PT  - JOURNAL ARTICLE
AU  - Emma S Lucas
AU  - Pavle Vrljicak
AU  - Joanne Muter
AU  - Maria M Diniz-da-Costa
AU  - Paul J Brighton
AU  - Chow-Seng Kong
AU  - Julia Lipecki
AU  - Katherine Fishwick
AU  - Joshua Odendaal
AU  - Lauren J. Ewington
AU  - Siobhan Quenby
AU  - Sascha Ott
AU  - Jan J Brosens
TI  - Recurrent pregnancy loss is associated with a pro-senescent decidual response during the peri-implantation window
AID  - 10.1101/368829
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 368829
4099  - http://biorxiv.org/content/early/2019/12/09/368829.short
4100  - http://biorxiv.org/content/early/2019/12/09/368829.full
AB  - Breakdown of the feto-maternal interface in early pregnancy causes miscarriage. The cycling endometrium becomes poised to transition to a pregnant state during the midluteal implantation window, coinciding with differentiation of stromal cells into decidual cells (DC) and emergence of senescent decidual cells (snDC). Emerging evidence suggests that DC engage uterine natural killer cells to eliminate their senescent counterparts, thus enabling formation of a robust decidual matrix in pregnancy. To examine if failure to constrain snDC during the peri-implantation window increases the risk of miscarriage, we reconstructed the decidual pathway at single-cell level in vitro and demonstrated that, without immune surveillance, secondary senescence rapidly transforms DC into progesterone-resistant cells that abundantly express extracellular matrix remodelling factors. Additional single-cell analysis of midluteal endometrium identified DIO2 and SCARA5 as marker genes of a diverging decidual response in vivo. Finally, we report a conspicuous link between a pro-senescent decidual response in luteal phase endometrium and recurrent pregnancy loss, suggesting that pre-pregnancy screening and intervention may reduce the burden of miscarriage.